PledPharma : and RTT agree to join forces

PledPharma and RTT agree to join forces

Creating a new specialised late-stage orphan drug development company

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Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

1. Appendix

3 |

Today's presenters

Nicklas Westerholm

CEO

Selected experience

• International experience from 20 years within AstraZeneca, from roles such as VP Project and Portfolio CVMD, VP Japan Operations, Investor Relations,
• Board member, Spago Nanomedical

Peder Walberg

Founder and CEO

Selected experience

• Founder and CEO, Medical Need
• Head of Business Development and Strategy, Swedish Orphan International and SOBI
• BoD of Wilson Therapeutics and identified Decuprate for treatment of Wilson disease

Previous experience

Previous experience

4 |

Creating a specialised late-stage orphan drug development company

1

3

5

Dedicated orphan drug development company with two late-stage orphan drug assets: Aladote® and Emcitate®

2	Highly attractive orphan drug segment with potential USDbn market opportunities

Clear path to market with plan to launch in EU and US through niche marketing organisation within 3 years

4	Combined core expertise from PledPharma & Rare Thyroid Therapeutics in late-stageorphan
clinical development, registration and launch

Executive leadership team with experience from:

5 |	Note: Under name change to Egetis Therapeutics

PledPharma and Rare Thyroid Therapeutics merge to launch a new company for late-stage orphan drug development

PledPharma

• Team with profound late-stage drug development experience and strong track-record
• Listing on Nasdaq Stockholm provides access to public markets and capital as well as visibility
• Desired prospective partner in project collaborations. Previous major license agreement with Solasia
• Efficient internal organisation and strong corporate governance

Synergistic orphan drug focus

• 2020 accelerated PledPharma's strategic review
• Lead asset Aladote® facilitates the new pronounced strategic focus on orphan drug segment
• Emcitate® and RTT's capabilities fit well with the new strategy
• Build critical mass, generate synergies and improve operational effectiveness for projects in the orphan segment
• Size, vicinity and complementary capabilities allow for a fast and smooth integration

Rare Thyroid Therapeutics

• Team with strong track-record of identifying and developing ODDs and creating shareholder value
• Strong network of external project advisors with specialist knowledge. Collaboration with Erasmus Medical Center in Rotterdam
• Founding team with experience from international launch and commercialization of orphan drugs

The combination of unique management expertise and multiple programs will drive synergies

6 |	Note: Under name change to Egetis Therapeutics

Key terms, conditions and timeline

Acquisition

Terms of the

acquistion

Acquisition

financing2

Rights issue2

Anticipated

timing

• PledPharma to acquire all outstanding common shares in Rare Thyroid Therapeutics
• Total offer consideration consists of a combination of PledPharma common shares and cash
• Owners of Rare Thyroid Therapeutics will receive a royalty of 3% of net sales generated through Emcitate®1
• Owners of Rare Thyroid Therapeutics will also be granted 50% of the net proceeds from a potential sale of US Rare Pediatric Disease Priority Review Voucher related to Emcitate®
• An upfront cash payment of SEK 60m
• PledPharma to issue approx 63.8 million shares representing 41% of the total number of outstanding shares in PledPharma post-transaction (incl. the contemplated rights issue of c. SEK 200m)
• A fully underwritten rights issue of c. SEK 200m with an overallotment option of c. SEK 50m
• Subscription price of SEK 5.25 per share corresponding to a 2.5 percent premium to close 2 October 2020
• Pro-ratasubscription commitments of c. SEK 64m from: the Fourth National Pension Fund (AP4), Nortal Investments AB (Staffan Persson), Cidro Förvaltning (Peter Lindell) (the company's three largest shareholders) as well as Chairman Håkan Åström and CEO Nicklas Westerholm
• Underwriting commitments of c. SEK 136m from: the Fourth National Pension Fund (AP4), Cidro Förvaltning (Peter Lindell), Chairman Håkan Åström and NYIP (Nyenburgh Holding BV)
• The share issue will be used to finance: (i) the development of Emcitate® and Aladote® to market approval in Europe and USA (60%); (ii) initial commercial preparations (20%); (iii) general corporate purposes and financial flexibility (20%)
• Launch of transaction (SPA signed): 5 October 2020
• EGM approval: 28 October 2020
• Record date: 2 November 2020
• Subscription period: 9-23 November 2020
• Outcome of transaction: 26 November 2020

7 |	Note: (1) Royalties of 10% on Emcitate® net sales to Erasmus Medical Centre; (2) Subject to EGM approval 28 October 2020

Orphan drug segment represents a highly attractive opportunity

1	Orphan drug designation is awarded to products
targeting limited disease populations1	Development
2	More than 7,000 known rare diseases
		Registration
3	Approx. 10% of the general population may be
affected by a rare disease
4	Substantial unmet medical need for patients, only	Market
5% of rare diseases have an approved therapy

• Less extensive clinical trials
• Agile and faster development process
• Lower costs
• Lower development risk
• Free regulatory advice
• Reduced fees
• Expedited review
• Market exclusivity
• No or few competitors
• Highly focused target groups
• Premium pricing

Well-defined patient populations with substantial unmet medical need

8 |	Note: (1) Populations of less than 5/10,000 inhabitants in the EU or <200,000 inhabitants in the US

Combining two highly promising orphan drug candidates in one company

Emcitate®

Therapy for genetic disturbance in thyroid hormone signalling with life-long severe disability

• Lead candidate for addressing MCT8 deficiency, a condition with high unmet medical need and no available treatment
• Rare disease which affects 1:70,000 males,
• Obtained Orphan drug designation in the EU and US 2017 and 2019 respectively. Potentially eligible for Rare Paediatric Disease Designation
• Phase IIb clinical trial completed with significant and clinically relevant effects
• Pivotal Phase IIb/III early intervention trial in young subjects planned to start H2 2020
• No competing products in clinical development

Aladote®

Prevents acute liver injury caused by paracetamol poisoning

• Paracetamol poisoning is one of the most common overdose with approx. 135.000 hospital admissions in US/EU5 per annum
• No adequate treatment for increased risk patients exists
• Orphan drug designation (ODD) granted in 2019 in the US
• Eligible for ODD in the EU as a results of Brexit, application under development
• Successful results from Phase Ib/IIa study in paracetamol overdosed patients
• Pivotal Phase IIb/III study planned for marketing authorisation application in both US and EU, ongoing interactions with the regulatory agencies (FDA, EMA and MHRA) to finalize study specific details
• No competing products in clinical development

9 |

Late-stage orphan drug pipeline addressing billion dollar markets

	Candidate	Pre-clinical	Phase I	Phase II	Phase III	Approval
	Emcitate®				Phase IIb/III
	Aladote®				Phase IIb/III
						* Phase III POLAR program for
						PledOx® was recently
	*PledOx®				Phase III	prematurely stopped. Results
				expected in Q4 2020 will
						determine if further
						development is warranted via
						strategic partnership/s

Rare Thyroid's candidate Emcitate®

PledPharma's candidate Aladote®

10 |

Upcoming pipeline milestones

• FPFV pivotal	• LPFV pivotal	• 12m interim	• Filing EU/US	• First EU/US
Phase IIb/III early	Phase IIb/III early	analysis Phase		approval
intervention trial	intervention trial	IIb/III early		and launch
Emcitate®		intervention trial

		2020		2021	2022	2023	2024
	Aladote®
		• Regulatory	•	Initiate pivotal	• Interim analysis	• Filing EU/US	• First EU/US
		interactions FDA		Phase II/III study			approval and
		& EMA	•	Orphan Drug			launch
				designation EU
	PledOx®	Results Phase III POLAR
		program in Q4 2020

11 |

Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

1. Appendix

12 |

EmcitateAladote

MCT8 deficiency a detrimental condition with significant unmet medical need

What is MCT8 deficiency?

What does it mean?

What are the challenges?

How do you manage the disease?

• Genetic disorder resulting in impaired thyroid hormone trafficking across cellular membranes
• Mutation located to the X chromosome, affecting only males
• Estimated prevalence of 1:70,000 males
• Too high and too low thyroid hormone stimulation in different tissues
• MCT8 deficiency leads to low or no thyroid hormone levels in the brain
• Compensatory increase in circulating thyroid hormone affects other organs e.g. heart, liver, kidney
• Initial symptoms appear within the first months of life, including muscle hypoplasia, hypotonia, spasms and seizures with severe neurocognitive disability
• Most patients never develop ability to sit or walk and remain dependant on caregivers throughout their entire life
• Currently no therapy available to address the underlying thyroid hormone trafficking defect
• Standard therapeutic approaches for thyroid dysfunction not effective
• Significant unmet medical need from a humanitarian, health economic and societal perspective

13 | Source: Groeneweg et al; Lancet D&E 2020, Schwarz et al; Clin Endocrinol & Met 2007

EmcitateAladote

Orphan drug candidate with clear scientific and mechanistic rationale and established safety profile

Difference normal MCT8 and deficiency of MCT8		Emcitate (tiratricol) - Addressing the MCT8 deficiency

• Thyroid hormone T3 requires transporters such as MCT8 to enter the target cells

Normal MCT8

• Functional thyroid gland producing T3
• Functioning production of MCT8

• T3 cross the cellular membrane and enters the

target cell	✓

• Tiratricol is a thyroid hormone analogue with high chemical and structural similarity to T3
• Unlike T3, tiratricol can cross cellular membranes without a functional MCT8 transporter
• Tiratricol can bypass the problem in patients with MCT8 deficiency, enter MCT8 deficient cells and restore thyroid hormone signalling
• Experience from 40 years on the French market in a different indication, owned and controlled by company

Emcitate in action

Cellular membrane

Mutated MCT8

• Functional thyroid gland producing T3
• MCT8 deficiency leads to absence or loss of function

of MCT8 on the cell surface

• T3 cannot cross the cellular

membrane and fails to enter
the target cell	

T3



MCT8

If deficiency of MCT8, the T3 is  unable to be transported across

the cellular membrane to enter the target cell

Tiratricol

TR

Tiratricol

With use of Emcitate (Tiratricol)✓

Tiratricol the thyroid hormone is able to enter the cell without MCT8

14 |

Overview of completed Phase IIb

EmcitateAladote

Primary objective

and results

Secondary

objective and

results

Description

Endpoints

• Evaluate the efficacy and safety of oral administration of tiratricol in male patients with MCT8 deficiency of all ages
• Highly significant primary outcome
• Significant and clinically relevant effects observed across secondary endpoints
• An international, single-arm,open-label, Phase II trial
• ClinicalTrials.gov identifier: NCT02060474
• Change in T3 serum concentrations
• Change in other thyroid hormone function tests
• Change in thyrotoxic symptoms and markers

• of patients
  Timetable

• 46 MCT8 patients in 9 countries
• Initiated in October 2014 (first patient in)
• Completed in June 2018

Encouragement to file product based on data from Phase IIb from EMA SAWP1) at protocol assistance meeting in July 2018

15 | Source: Groeneweg et al, Lancet D&E 2019; Note: (1) European Medicines Agency, Scientific Advice Working Party

EmcitateAladote

Consistent and highly significant results in completed Phase IIb trial

Serum T3 (nmol/l)

10

T0

T12

8	p < 0.0001

6

4

2 Normal range

0

	Endpoints	Baseline mean (± SD)	12 months mean (± SD)	Difference in means (95% CI)	p-value
	Serum T3 (nmol/L)	4.97 (± 1.55)	1.82	(± 0.69)	-3.15(-3.62,-2.68)	<0.0001
	Weight to age (z score)	-2.98(± 1.93)	-2.71(± 1.79)	0.27 (0.03, 0.50)	0.025
	Resting heart rate (bpm)	112 (± 23)	104	(± 17)	-9	(-16,-2)	0.01
	Mean heart rate 24 h (bpm)	102 (± 14)	97	(± 9)	-5 (-9,-1)	0.012
	SHBG (nmol/L)	212 (± 91)	178 (± 76)	-35	(-55,-15)	0.0013
	Total cholesterol (mmol/L)	3.2 (± 0.7)	3.4	(± 0.7)	0.2	(0.0, 0.3)	0.056
	CK (U/L)	108 (± 90)	161	(± 117)	53(27, 78)	<0.0001

16 | Source: Groeneweg et al; Lancet D&E 2019

EmcitateAladote

Indication of positive effect on neurocognitive development in the youngest patients

GMFM score (%)1)

40

30

20

10

0

#

1.5 to <4 years

T0

T12

#

#

Patients

	4 to <10 years				≥10 years

Age at baseline

17 | Source: Groeneweg et al; Lancet D&E 2019

EmcitateAladote

Planned Phase IIb/III early intervention trial design

Primary objective

Secondary objective

Description

Endpoints

# of patients

Preliminary timetable

• Improvement of neurocognitive development
• Achievement of motor milestones (e.g. hold head, sit independently)
• Confirm findings from Triac I Trial in youngest age group
• An open label, multi-centre trial in very young children with MCT8 deficiency
• International trial with 10 centres in both Europe and North America
• Design discussed and anchored with EMA and FDA
• Improvement in neurocognitive development as measured by GMFM1) and BSID-III2) compared to natural history controls
• Achievement of motor milestones
• Normalisation of thyroid hormone function tests and markers of thyrotoxicosis
• 15-18children 0-30 months of age
• Regulatory approval in place in all markets: CZ, DE, IT, UK, FR, NL, US
• Start pending COVID situation, FPFV3 presently expected in H2 2020, LPFV4 in H2 2021
• Results from interim analysis at 12 months expected in H2 2022

18 | Note: (1) Gross motor function measure; (2) Bayley Scales of Infant Development; (3) First patient first visit; (4) Last patient first visit

EmcitateAladote

Clinical development timeline

✓•	Acquisition of all	•	CTA approvals in EU
	rights and assets	•	IND submission	•	Launch preparations
	relating to Teatrois	•		•
	in France	IND open (SMP)	Filing EU MAA and US
✓•	Triac I Trial	•	FPFV2 pivotal Phase		NDA
•
	completed		IIb/III early	Interim (12 month)
2018		2020	intervention2022/23trial	2022	analysis3
✓•	EMA Protocol
	Assistance

✓•	Licensing of IP,	✓•	US Orphan Drug		• Completed
2017	data and know-how	2019	Designation	2021	recruitment (LPFV)
within thyroid	Publication Triac	Triac Trial II
	hormone signalling	✓•
		Trial
	disorders from
	Erasmus Medical	✓	FDA pre-IND meeting
		•

2023

• EU and US approval,

Centre 1

✓• EU Orphan Drug

Designation

✓• CTA submissions EU

pricing and launch

• Publication of

complete study data

(24 month)

✓• Elected for funding by

EUREKA EUROSTARS

19 | Note: (1) Erasmus Medical Centre; (2) First patient first visit; (3) Provided compelling data in 12 month interim analysis of Phase IIb/III early intervention trial

Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

1. Appendix

20 |

EmcitateAladote

Paracetamol poisoning - no adequate treatment for increased-risk patients

What is paracetamol poisoning?

How many does it affect?

Why is current treatment inadequate?

A new standard of care is needed

• Minimum toxic dose of paracetamol in adults is only 7.5g
• Risk factors include malnutrition, alcoholism and consumption of other medications
• Paracetamol poisoning can lead to acute liver failure, liver transplant or death
• 19 billion units of paracetamol packages are sold in the US alone every year
• 89,000 cases/year of paracetamol overdose in the US and 105,000 cases/year in the UK
• ~50% of paracetamol overdose cases are unintentional
• Efficacy of current NAC (N-acetylcysteine) treatment decreases with time
• Approximately 25% of patients are late arrivals to hospitals (>8h) - late arrivals are at increased risk
• There is no effective treatment option for patients at increased risk
• Aladote® aims to become a new standard of care for patients with increased risk for liver injury in combination with NAC

21 |

EmcitateAladote

Orphan drug candidate with clear scientific and mechanistic rationale

Early presenters (<8h)		Late presenters (>8h) are at increased-risk for liver injury
NAC treatment effective against liver injury		NAC treatment + Aladote® to prevent liver injury
• Liver glutathione (GSH) replenished by NAC, toxic NAPQI metabolite excreted as		• Under NAC treatment alone liver GSH stores depleted by the toxic NAPQI
GSH conjugate		metabolite -> oxidative stress, mitochondrial dysfunction and liver injury
		(necrosis)

• In most cases NAC effectively prevents liver injury i.e. limited need for Aladote®	• Aladote® (calmangafodipir) prevents ROS and RNS formation, restores
	mitochondrial energy production and prevents liver injury

22 | Source: Burke et al. 2010

EmcitateAladote

Overview of completed Phase Ib/IIa

Primary outcome

Secondary outcomes

Description

Endpoints

• of patients
  Timetable

• Safety and tolerability of Aladote® co-treatment with NAC
• Alanine transaminase (ALT), international normalised ratio (INR), keratin- 18, caspase-cleavedkeratin-18 (ccK18), microRNA-122 and glutamate dehydrogenase (GLDH)
• An open label, rising-dose, randomized study exploring safety and tolerability of Aladote® co-treatment with NAC
• ClinicalTrials.gov identifier: NCT03177395
• Adverse Events and Serious Adverse Events
• Secondary endpoints such as ALT and biomarkers of liver damage
• Single ascending dose study in 3 dosing cohorts of 8 patients (N=24) as add- on to NAC regime
• Initiated in June 2017 (first patient in)
• Completed in September 2018

23 |

EmcitateAladote

Positive proof-of-principle Phase Ib/IIa results

Safety & tolerability		Liver injury - ALT1 pre-defined secondary outcome

		NAC +	NAC +	NAC +
Event	NAC	2	5	10
alone	μmol/kg	μmol/kg	μmol/kg
		Aladote	Aladote	Aladote
Any AE	6 (100%)	6 (100%)	6 (100%)	6 (100%)
Any SAE	2 (33%)	4 (67%)	2 (33%)	3 (50%)
SAE
starting	1 (17%)	1 (17%)	1 (17%)	2 (33%)
within 7
days

• Met primary endpoint of safety tolerability in the combination of Aladote® and NAC
• No AE or SAE probably or definitely related to Aladote®

			NAC +	NAC +	NAC +
Event		NAC		2		5	10
alone	μmol/kg	μmol/kg	μmol/kg
			Aladote	Aladote	Aladote
50% ALT	2	(33%)	0	(0%)	0	(0%)	1 (17%)
increase
100% ALT	1	(17%)	0	(0%)	0	(0%)	1 (17%)
increase
ALT >100
U/L at 10	2	(33%)	0	(0%)	0	(0%)	0 (0%)
hours
ALT >100
U/L at 20	2	(33%)	0	(0%)	0	(0%)	0 (0%)
hours

• ALT >100 U/L is the indication to stay in hospital

• of patients needing additional NAC infusions after planned 12h NAC infusion

50%

11%

NAC alone	NAC + Aladote
(n=3)	(n=2)

24 |	Note: (1) Alanine transaminase (ALT) is a transaminase enzyme also called alanine aminotransferase (ALAT). ALT is found in plasma and in various body tissues especially the liver's hepatocytes. Serum ALT is commonly measured clinically as
	part of a diagnostic evaluation of hepatocellular injury, to determine liver health

EmcitateAladote

Aladote® demonstrates consistent results of reduced liver injury as measured by exploratory biomarkers

K18				ccK18
	10					10
frombaseline				NAC alone	baselinefrom			NAC alone
				NAC and 2umol/kg				NAC and 2umol/kg
changeRelative	1			NAC and 5umol/kg	changeRelative	1		NAC and 5umol/kg
		NAC and 10umol/kg
						NAC and 10umol/kg
	0.1					0.1
	0	10	20
			0	10	20

Time (hours)	Time (hours)

miR-122
	10
baseline			NAC alone
from			NAC and 2umol/kg
changeRelative	1		NAC and 5umol/kg
	NAC and 10umol/kg
	0.1
	0	10	20

Time (hours)

• K18 and its caspase cleaved form ccK18, is a measure of cell death and correlate with peak ALT activity during the hospital stay
• miR-122is a liver specific early marker (micro-RNA) for acute liver injury which predicts a rise in ALT activity following paracetamol overdose
• Results of these biomarkers provides scientific support to suggest that Aladote® may reduce liver injury when added to NAC compared to NAC alone

Note: miR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose. In paracetamol overdose, 25 | the full-length variant of K18 is released by necrotic cell death. A shorter, caspase cleaved form of K18 is released following cell apoptosis (programmed cell death). Both forms of K18, measured in the first serum sample at presentation at the hospital after paracetamol overdose,

correlate with peak ALT activity during the hospital stay. Full length K18 distinguished patients with and without acute liver injury at an early time where ALT activity was still normal

EmcitateAladote

Pivotal Phase IIb/III study for US/EU regulatory submission1

Patient population

NAC regimes

Initiation of randomized treatments

Treatment arms

Interim analysis

Sample size

Efficacy endpoints

• Increased-riskPOD patients, Late arrivals (>8h) requiring treatment with
  NAC
• Licensed 21 hr NAC regime
• IV (bolus) as soon as possible after randomization and after starting NAC (but no later than 4 hours after starting NAC)
• 3 arms: Aladote® high-dose; Aladote® low dose; Placebo
• Interim analysis after 50% of patients, that includes a futility analysis and dose selection where the most effective dose will be continued
• 225 patients planned
• Primary: Composite of ALT and INR
• Number (%) of patients that need further NAC after 21h
• Length of hospital stay
• Experimental biomarkers, K18, miR-122 and GLDH

	Study countries	• EU and US

26 | Note: (1) Tentative study design, pending ongoing regulatory interactions to finalize specific study details

EmcitateAladote

Aladote® clinical development timeline

• US ODD granted
• Results presented at Society of Toxicology, EASL ILC and Lancet

	EBiomedicine	•	Interim analysis	20321
2019	✓ Regulatory	2022/23 •	Regulatory

	interactions with	submissions EU/US
	FDA and EMA

	✓	Phase Ib/IIa study	•	Regulatory
			interactions FDA &
		fully recruited
2018		2020/21	EMA	2023/24 • First EU/US
✓
Initial Phase Ib/IIa
		•	Initiate pivotal	approval and launch
		results
			Phase II/III study
	✓ Established
	•	Orphan Drug
		Scientific Adviosry

Board	Designation EU

• Full Phase Ib/IIa results
• Submission of ODD

27 | Note: (1) Calmangafodipir composition of matter patent expiresc

Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

1. Appendix

28 |

EmcitateAladote

Orphan drugs provide an attractive return on investment

Shorter clinical development time1		Higher attainable prices2
				Mean cost per patient and year (USDk)
Phase II to launch											152,2	150,9
			143,4

Orphan drugs provide attractive returns5

Average # of years		134,5
		128,1
ORPHAN	3.8
	years
	5.4	23,8	28,2	31,2	32,4	33,7
NON-ORPHAN
	years
		2014	2015	2016	2017	2018

1.7x

10,3%

			Non-orphan Orphan
Higher probability of success3	Fewer patients required for clinical trials4
		Patients per trial	Non-orphan	Orphan
Phase III to approval	800
POS in metabolic/endocrinology indications	700
		600
		500
		400
51.6%	77.8%	300
200
		100
		0
ALL DRUGS	ORPHAN DRUGS	Phase I	Phase II	Phase III

6,0%

Return on investment

Non-orphan		Orphan

29 |	Source: (1) Orphan drugdevelopment: an economically viable strategy for biopharma R&D, Meekings, Williams & Arrowsmith, 2012; (2) EvaluatePharma; (3) Estimation of clinical trial success rates and related parameters, C. Wong, K. Siah, A.
Lo, Biostatistics, 2019; (4) BioMed Central; (5) EvaluatePharma Orphan Drug Report 2013

EmcitateAladote

Emcitate® and Aladote® - alleviating societal burden

Emcitate®		Aladote®

All MCT8 patients have		A recent study in a condition
significant neurocognitive		with similar severity (SMA)		In the US the annual cost in		The POD Emergency
disability from early		estimated total healthcare		2010 was estimated at		Department and inpatient
childhood and typically		cost (excluding treatment		USD 1,059m to treat patients		cost is approximately
require constant, life-long		cost) to USD 138k per patient		with POD3		USD 13-40k3
supportive care		and year1

		Patients underweight for age		The average POD inpatient
Median life-expectancy of		or without ability to hold		length of stay is 3.1 days with		US liver transplant costs
MCT8 patients is 35 years2		head have an even increased		a variance of +4.4 days for		USD 125-473k3
		risk of premature death		the most severe cases3

30 |	Source: (1) Economic burden of spinal muscular atrophy in the United States: a contemporary assessment, Droege et al, Journal of Medical Economics, 2020; (2) Disease characteristics of MCT8 deficiency: an international, retrospective,
multicentre cohort study, Groeneweg et al, The Lancet, 2012; (3) Adapted from: Altyar A. Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA BMJ Open 2015;5;

EmcitateAladote

Orphan drug pricing landscape

2018 US pricing of non-oncology orphan drugs with remaining protection

US Revenue per patient per year (USD)

>600 000

1. 000

1. 000

1. 000

1. 000

1. 000

1. 000
   0

Brineura

Strensiq

Soliris

Spinraza

*Emcitate®

Average price of USD 150 000

Neulasta

*Aladote®

0

20 000

40 000

60 000

80 000

100 000

120 000

140 000

160 000

180 000

US No. of patients per year

31 |	Note: (*) Expected price points for Emcitate® and Aladote®; Source: EvaluatePharma. FDA Orphan drug designations and approvals database (Downloaded 9 March 2020). Prevalence according to Genetics Home Reference - NIH U.S. National
Library of Medicine for underlying conditions for Brineura, Naglazyme and Strensiq.

EmcitateAladote

Late-stage orphan drug pipeline - a billion USD opportunity

Emcitate®		Aladote®

Target population

10-15,000

1:70.000 males affected1, 1.5bn people with access to western standard health care2

Pricing assumption	Target population
200-400,000	~135,000
USD/per patient per year	Hospital admissionsPOD
in the US	patients in US and
	EU5/year

Pricing assumption

~5,000

USD/dose in the US

COGS assumption3	COGS assumption4
Low	Low
single digit	single digit
percent	percent

32 |	Source: (1) 1:50,000-70,000. Visser et al, Clinical Endocrinology 2012; (2) RoW approachable population including Australia, Canada, Japan, Russia, Switzerland, South Korea and Turkey; (3) Based on price assumption of 200,000 USD per patient
and year; (4) Based on price assumption of 5,000 USD; Note: Royalties of 10% on Emcitate® net sales to Erasmus Medical Centre

EmcitateAladote

Niche market characteristics enable a small and focused commercial footprint

Strong success factors…
1	High unmet medical need without competing
compounds
2	Centralized, focused target groups of specialists
3	Top-downscientific sales approach
4	Leading KOL support
5	Treatment algorithms highly protocol driven

…for sustainable, profitable & lean commercialisation

Plan to build inhouse commercial capabilities for launch of Emcitate® and Aladote® in EU and US

Small and focused footprint with an estimated < 50 FTEs considered sufficient for both assets

Retain larger share of product revenues over time within company

Commercialization in other territories through partners

33 |

Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

1. Appendix

34 |

Creating a specialised late-stage orphan drug development company

1

3

5

Dedicated orphan drug development company with two late-stage orphan drug assets: Aladote® and Emcitate®

2	Highly attractive orphan drug segment with potential USDbn market opportunities

Clear path to market with plan to launch in EU and US through niche marketing organisation within 3 years

4	Combined core expertise from PledPharma & Rare Thyroid Therapeutics in late-stageorphan
clinical development, registration and launch

Executive leadership team with experience from:

35 | Note: Under name change to Egetis Therapeutics

Agenda

1. Creating a new specialised late-stage orphan drug development company
2. Emcitate® - clinical development programme
3. Aladote® - clinical development programme
4. Commercial opportunity and path to market
5. Summary

A Appendix

36 |

Leadership team

Nicklas Westerholm

CEO

• Took office in June 2017 and has previously worked in the AstraZeneca Group since 1995 in several global roles in various business areas, most recently as VP Project & Portfolio Management. Prior Nicklas has held positions such as Executive Officer & VP Japan Operations, Director Investor Relations, Head of Global API Supply and Head of Development Manufacture. He has studied Analytical and Organic Chemistry at Stockholm University and Chemical Engineering at KTH, as well as studies at University of Warwick, INSEAD and Harvard Business School.
• Ownership: 16,000 shares and 500,000 warrants

Marie-Louise Alamaa

Interim CFO

• Extensive experience within finance and controlling from public companies. Her previous positions include CFO at Index Invest International AB, various senior finance positions at Crucell Sweden AB (previously SBL Vaccin AB) and Senior Consultant at the listed gaming company Stillfront Group AB. She has studied Economics at the Universities of Uppsala and Stockholm, Sweden, with a particular focus on accounting and auditing

Christian Sonesson

VP Product Strategy & Development

• Appointed VP Product Strategy & Development in August 2017 following 13 years at Astra Zeneca. He has broad experience within drug development, including successfully leading products during Phase 3 (FORXIGA® in type 1 diabetes) and of regulatory submissions and defense, bringing new drug candidates to market in different regions (e.g. FORXIGA® in type 2 diabetes, MOVANTIK®, ONGLYZA®-SAVOR,BRILINTA®-PEGASUS and QTERN®). PhD in Biostatistics from Gothenburg University and an Executive MBA from Stockholm School of Economics.
• Ownership: 200,000 warrants

Stefan Carlsson

CMO

• Took office as CMO in November 2017. Med Dr Gothenburg University, where he also has a doctorate in physiology. He has a long experience from leading positions in preclinical and clinical drug development and has published 30 scientific articles in the fields of pharmacology and physiology. Prior to PledPharma , he held positions at AstraZeneca as clinically responsible globally for several products in the market and under development, including Crestor® and Epanova®.
• Ownership: 250,000 warrants

Jacques Näsström

CSO

• Pharmacist with a Ph.D. in Pharmacology from Uppsala University and with an MBA from the Stockholm School of Economics. He has more than 30 years of experience in the pharmaceutical and biotechnology industry, including a position as Investment Manager at Karolinska Investment Fund and various positions in early drug research at Astra and AstraZeneca. CEO of PledPharma between 2010 and June 2017, before that, Jacques worked as research director at Q-Med AB between 2006-2010
• Ownership: 80,452 shares and 20,000 warrants

37 |

Scientific advisory board

Established for Aladote®

Dr. Richard C. Dart

• Ph.D., Chair of the Department of Medical Social Sciences at Northwestern University Feinberg School of Medicine in Chicago, USA. Expert in evaluations of patient-reported outcomes in clinical trials.

Professor Laura James

• MD, Associate Vice Chancellor for Clinical and Translational Research and Professor of Pediatrics at the University of
  Arkansas for Medical Sciences (UAMS) and Arkansas Children's
  Hospital System, USA.

Peter De Paepe

• MD, Professor in clinical pharmacology at the Heymans Institute of Pharmacology at Ghent University, and is currently head of the emergency department of the Ghent University Hospital in Belgium.

Established for PledOx®

Professor Guido Cavaletti

• MD, Ph.D. and Head of the Neuroimmunology Center at S. Gerardo Hospital and the Experimental Neurology Unit at the School of Medicine, University of Milan-Biocca in Monza, Italy and international expert in chemotherapy induced peripheral neuropathy.

Professor Emeritus Bengt Glimelius

• MD, Ph.D. Professor emeritus in oncology at the University of Uppsala and Consultant at the University hospital. Coordinating principal investigator in the PLIANT trial - PledPharma's Phase IIb Study with PledOx®.

Associate Professor Rolf Karlsten

• MD, Ph.D. Specialist in anesthesiology, intensive care and neuropathic pain management. Head of Rehabilitation Medicine and Pain Center at Uppsala Academic Hospital.

Professor David Cella

• Ph.D., Chair of the Department of Medical Social Sciences at Northwestern University Feinberg School of Medicine in Chicago, USA. Expert in evaluations of patient-reported outcomes in clinical trials.

Fifth undisclosed member

• US expert and KOL In CIPN

38 |

Board of directors

Håkan Åström

Chairman of the board

• Board member since: 2011
• Other assignments: Chairman of the boards of directors of Affibody Holding AB, Tubulus RP Förvaltning AB and MedCore AB. Board member of Ferrosan Medical Devices A/S and Rhenman & Partner Asset Management
• Ownership: 505,337 shares and 192,000 warrants

Sten Nilsson

Board member

• Board member since: 2013
• Professor in oncology with affiliation to the Karolinska Institute (KI), MD, Ph.D.
• Other assignments: Board member of the Swedish Cancer Society Research Council and Rhenman & Partner Asset Management
• Ownership: 1,100 shares and 35,000 warrants

Peder Walberg

Incoming Board member*

1. Appointment subject to EGM approval 28 October 2020
   ▪ Founder and CEO of Rare Thyroid Therapeutics
   ▪ Other assignments: Board Member of Immedica Pharma AB

Gunilla Osswald

Board member

• Board member since: 2017
• Ph.D. in biopharmacy and pharmacokinetics
• Other assignments: CEO BioArctic AB
• Ownership: 50,000 warrants

Elisabeth Svanberg

Board member

• Board member since: 2017
• MD, Ph.D., Assoc Professor in surgery
• Other assignments: Chief Development Officer Ixaltis SA. Board member Swedish Orphan Biovitrum (SOBI)
• Ownership: 96,000 warrants

39 |